E-mail Back from Doctor Who Has Worked With Retroviruses for 35 Years

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Mya Symons

I was not sure where to post this. I was looking at the medical and science journal abstracts and I noticed that one of the doctors often mentioned had the same last name as me. This is unusual because my last name is not common. We are probably related in some way. Anyway, he was kind enough to e-mail me back very detailed answers to my questions. He has a Ph. D. in Biochemistry and Biophysics and has worked with retroviruses for many years. I believe he also worked on the human genome project and served as an editor to one of the virology journals.

One thing I am confused about: Did the NIH and FDA study prove that there are several variations of MuLv related viruses, even within the same person? I thought it did. I think he is saying he believes there are not many variations. --he says they "have not evolved"

Here is the e-mail

Hello. My name is Rebecca _____________. I hail from the MN __________ clan. I came across your name while attempting to read some medical journal reports on retroviruses. My husband, my son, and I have been sick for several years with CFS/ME (Chronic Fatigue Syndrome/Myalgic Encephalitis) and/or fibromyalgia. I see your interest is retroviruses. I was wondering if you have been following the research on XMRV. Have you read the recently released NIH and FDA study? Do you think that XMRV or MuLv related retroviruses could possibly be the cause of the illness associated with some cases of Chronic Fatigue Syndrome and Fibromyalgia or could be one of the causes? Do you believe that it is possible for a mouse retrovirus to be passed to humans or is this too far of a jump?

Dear Rebecca,

While it is very much of a pleasant surprise to get an email from another ____________ it is painful to know the circumstances. I can only imagine how frustrating such an illness is.

I have been in the retrovirus field for 35 years, although most of our work is with HIV. We do have a small epidemiology study with XMRV we are trying to do. My guess is it will be negative as we will be looking at blood plasma samples (aka samples of convenience). I know most of the people in this new field, especially the ones who themselves have been in the retrovirus field for awhile.

Your questions are right on mark. I haven’t read the papers carefully yet but I have seen the data from a number of studies at recent meetings. Given the medical importance there has been a lot of work in a relatively short period of time. To be honest, I have never seen a field reach such a level of confusion so quickly. Remember, this field started as being involved with prostate cancer. Given the claims going around I am impressed with your willingness to be cautious in what you believe.

The X in XMRV stands for xenotropic. This is an odd set of retroviruses that have been found in the mouse genome. At some point these viruses infected mice (and being retroviruses some of them wound up as part of the mouse genome). Along the way certain mice developed mutations in the receptor for the virus and at that point the virus could no longer infect these mice even though the viral genome was still part of the mouse genome. These viruses, when induced from mouse cells, can infect cells of other species, thus the name xenotropic. Yes, they can infect human cells. Can they infect humans? I don’t know, there is way more biology in infecting an entire organism and persisting in a population.

There are good reasons to worry about XMRV being a false positive result. Many labs grow mouse cells and human cells in the same incubator and by chance there may have been contamination (a pipet used to take the tissue culture medium off of the mouse cells that was accidently used to put medium on the human cells would be enough to transfer the virus from the culture of mouse cells to the culture of human cells). Thus the detection of such mouse viruses in human cells in culture is suspect. Similarly, a favorite experiment is to put human tumors in mice and watch them grow (or try to cure them). These human cells would certainly get infected with the mouse xenotropic virus while in the mouse and this could wind up back in the lab incubator. Finally, the technique of polymerase chain reaction where we make many copies of DNA from a small number of copies so that we can detect it is famous for finding contaminants. There are plenty of reasons to be skeptical from the technique side. Conversely, when someone fails to find something is this just bad technique in another form? I tend to believe negative results from good labs, but it is hard to explain the positive results as all being lab contamination.

There is a meeting that is just being held on XMRV. I didn’t attend but I did get an email about a session summarizing the results from the meeting that will be put on the internet in real time and also archived. Based on your email I would guess that you will understand most of what is said so I encourage you to watch it. I am getting my lab together to watch it as I believe it will be the latest summary possible. Also, I know some of the panel members and they will give a thoughtful and fair interpretation.

I hope this is helpful. If you have more questions I would be glad to discuss them with you. I know lots about retroviruses. I am sorry but I don’t know much about CFS, but I guess I have lots of company there. If CFS is caused by a retrovirus then one class of the HIV drugs (called nucleoside analogs/chain terminators/NRTIs) should inhibit their replication. I suspect these are already being tested off label in CFS patients to see if there is any relief. If the results are positive it will be big news. If the results are negative we may not hear about it for awhile.

In less than a week the International Workshop on XMRV will take place in Bethesda, MD, USA. We are happy to invite those people who are not able to attend the workshop to tune in to a webcast Q & A session on Wednesday 8 September, 5.15 PM EDT / 11.15 AM CET. Please use the following link to get connected: XMRV Webcast <http://www.newsletter-ve.com/mail/link.php?M=26742&N=226&L=137&F=H> . For those who cannot watch the webcast live, an archive version will be available for viewing at this same website by week’s end.

This webcast Q&A wrap-up session will touch on the latest developments in the field in order to evaluate the state of our knowledge, address controversies, and develop an understanding between experts that will help direct future research.

The Q & A panel will consist of the following experts in the field of XMRV:

One of the things that I hope will happen soon is that a set of control samples get sent around to a number of labs. In this scenario someone creates a set of samples that are positive for XMRV and also some that are negative. These are coded then sent out and people are asked to test them and see if they can identify them correctly, the equivalent of a blinded taste test. This is going to be essential to start untangling the current state of confusion.

There are two more things that are perplexing. In studying HIV we have come to learn how rapidly a virus can evolve. The genome sequences from XMRV are surprisingly close to several distinct groups mouse viruses (called xenotropic and polytropic, the latter infects cells from many species including mice, unlike the xenotropic ones). This suggests they are not growing very much otherwise they would evolve between one person and the next. However, we have to admit we don’t know much about the evolution rates of these viruses even in mice, in contrast to all we’ve learned about HIV evolution. The other thing is that in mice these types of viruses are famous for causing tumors. As retroviruses, the viral genome is copied into DNA and inserted into the host cell DNA. This is a semi-random process. If the insertion happens by chance to be next to a host gene that controls cell growth then the inserted viral DNA can turn on that gene and cause the cell to start growing inappropriately. In fact, in the past we have used the position of the viral genome in the tumor cell DNA of experimentally infected mice to identify host genes involved in cancer (proto-oncogenes/i.e. normal genes that can be involved in cancer when inappropriately expressed or mutated). When the XMRV story started with prostate cancer everyone wanted to know “What are the host genes near the viral integration sites?” That is still an open question. However, we don’t know how XMRV could give rise to a CFS-type disease given what we know about what these viruses do in mice.

Senior Member

Good to hear another perspective, even if he's not been following it closely.

Emotionally, I'm still sceptical about XMRV... but it would be really hard to explain two positive papers without there being some link. Maybe it will just be far more complicated than the conneciton between HIV and AIDS (well - it must be with so many healthy positives).

My number one worry is still that it will be a complete bust, and all these nice bright researchers will have no further interest in CFS, leaving us back where we were with the quacks. It's such a relief to think that lots of good scientists are looking at CFS at the moment.

I know nothing

He seems like a very nice and understanding doc... this mail shows us two things: it seems the news of the discovery of XMRV and MLV- related viruses in ME/CFS has reached the main stream health practitioner , but they are not well informed and a lot more awareness has to be created to push for further research.
What i found astonishing is that a retrovirus specialist thinks XMRV can and is treated of label with retro viral already. That shows me, treating with of label drugs to see if the hypothesis sticks, is a common praxis and on the contrary to what many "psychobabble" health care provider babble about taking a risk and it is to early blablaba.... to treat with retro viral drugs of label is not a bad idea, if done under the right specialist supervision!

By the way, XMRV and MLVs are in a group which are called human gamma retroviruses.There are many MLVs related viruses and XMRV is one of them. Read Bob's blog , it is a good summary of all the different terms.

* XMRV is only found in laboratory mice fiddled with by scientists (See Dr Coffin's comments).
* Animal CELLS from laboratories have previously entered the human blood supply through government vaccination programmes. See HIV/Polio.
* XMRV/MULV is found in ME/CFS patients in very high numbers, who just happen to have neuro immune disease:

These percentage rates are this high, before even knowing the virus reservoir! (knowing where to look). Once knowing where to look they will of course be higher. (We need in addition to blood: tissue/CSF fluid tests to measure XMRV/MULV's, these have not been done yet in ME/CFS. The % findings are in their infancy and will only rise.

*XMRV has more positive studies coming out in 48hrs and the near future showing strong correlation to ME/CFS.

Blomberg
De Meirleir
Mikovits
Cheney
Another that Cort mentioned

*Contamination theory has been disproven by the CDC's Switzer back in 2009, and FDA in 2010.
This was important as due to being PCR, it could have been contamination (if not disproved, which it was). PCR is 'old hat', we now have other methods......

1)
We have CULTURE method to look for MULV/XMRV, and we have ANTIBODIES. Culture method takes your own fresh cell, and infects it with your own blood. Proving this is not contamination but a retrovirus living in your body infecting your own cells. End of argument.

2)
We have Antibody assays. It is physically impossible to have an antibody response to a contaminant.
So for the last time.... XMRV/MULV ANTIBODIES found in ME/CFS patients blood CANNOT BE CONTAMINATION.

If I know this and have no qualifications, this email from Rebecca_________ seems possible it could be a hoax to fool people who don't know basic science?

This Rebecca_______ email also comes on the eve of the 1st International Conference on XMRV that is about to reveal more and more direct links to XMRV/MULV's in ME/CFS

Make of that what you will.....either way it's too late. Everyone knows. Even uneducated people like me know. If I can understand then someone studying science for 35 years who has a Ph. D. in Biochemistry and Biophysics would know too.

Former CEO

Firstly great to hear he's so open-minded on it, and illustrative that such people will be watching the conference with great interest - if there are answers to some of these questions he's raised interest in the field should really take off. And a great contact to have, and to cultivate.

Regarding some of the open questions:

One of the things that I hope will happen soon is that a set of control samples get sent around to a number of labs. In this scenario someone creates a set of samples that are positive for XMRV and also some that are negative. These are coded then sent out and people are asked to test them and see if they can identify them correctly, the equivalent of a blinded taste test. This is going to be essential to start untangling the current state of confusion.

That's well under way, there's a 4-phase exercise, I can't think of how to track down the details though. But CDC, WPI, and other labs have been comparing notes in this way, details somewhere in the XMRV forums I expect. Last news on that was a few months ago, just after the CDC study came out I think. Can't remember any specific conclusions. Maybe he's thinking of a wider exercise; more likely he's unaware of that work.

There are two more things that are perplexing. In studying HIV we have come to learn how rapidly a virus can evolve. The genome sequences from XMRV are surprisingly close to several distinct groups mouse viruses (called xenotropic and polytropic, the latter infects cells from many species including mice, unlike the xenotropic ones). This suggests they are not growing very much otherwise they would evolve between one person and the next.

Certainly Alter/Lo found 4 related MLVs and said at the press conference that the spread of the gammaretrovirus family was characteristic of retroviral infection, strengthened the evidence for retroviral infection in CFS, and I think said it suggested they were evolving in human hosts. Perhaps he'd be a little less sceptical if he had had time read the paper in full.

His view on the difficulty of explaining the results by contamination is very encouraging. I agree, since the WPI used 3 separate labs, and Alter took great pains (and an extra 3 month delay) to eliminate contamination. Since the results are broadly comparable in terms of percentages I agree contamination looks less and less likely.

One final point I'd note is that there have actually been several more positive XMRV studies than just the 2 in CFS. A German group, an unpublished Japanese study, and I'm not sure how many prostate cancer studies but at least 2, all of these found background XMRV rates in controls, again all of them in the same range of 2-7%. Given all of that evidence, it really seems extremely likely to me that the negative studies - which found no XMRV whatsoever even in healthy controls - are just failing to detect. Since Alter didnt find XMRV specifically, but the related MLRs, and the negative studies were looking for XMRV specifically and not the polytropic variants, and since one of the UK negative studies did find evidence of the polytropic MLRs but disregarded that somewhat (until Alter's paper came out) because they were focused on XMRV, the evidence really does seem to be stacking up. The only kind of contamination explanation I can conceive of is if the positive studies were all using the same cell lines in some way - but I'm fairly sure it's been established they were not, and of course all the WPI labs and Alter's labs would have all had to systematically be looking at a very contaminated CFS process and a slightly contaminated control samples process...when he says it's hard to explain all the positive results as contamination, he's not kidding!

Former CEO

He seems like a very nice and understanding doc... this mail shows us two things: it seems the news of the discovery of XMRV and MLV- related viruses in ME/CFS has reached the main stream health practitioner , but they are not well informed and a lot more awareness has to be created to push for further research.
What i found astonishing is that a retrovirus specialist thinks XMRV can and is treated of label with retro viral already. That shows me, treating with of label drugs to see if the hypothesis sticks, is a common praxis and on the contrary to what many "psychobabble" health care provider babble about taking a risk and it is to early blablaba.... to treat with retro viral drugs of label is not a bad idea, if done under the right specialist supervision!

Good points aruschima, I picked up the same vibes. It really is extraordinary, when you get a neutral view like this, how incredibly distorted the "anti" camps arguments are. If it weren't for the conference coming up, I'd be saying we really need to be finding people like this and getting the info in front of them; as you say, they seem not to have even looked at it in any detail at all. Regardless of what your views on conspiracies are, it's very clear that for the vast majority of sceptics or the unconvinced, they simply haven't ever looked at it at all. It's all tucked away under psychiatry. No wonder they're so sceptical; the fact that the whole story is completely hidden from view is just too unbelievable!

How many times do you hear that nobody knows anything about CFS?! Both amongst researchers, clinicians, and the ordinary people I speak to, scarcely any of them have even heard of CFS! Occasionally there's a flicker of recognition (and sometimes a glazing over) when you mention ME. I then ask them whether they've heard of MS, and of course they all have. Then when I say there's about twice as many CFS as MS, I lose all credibility...that just can't be true...

We're simply invisible at the moment - out of the darkness, into the light!

An excellent summary of some very pertinent facts. The only thing I disagree with is your interpretation of what it means that you know more about it than doctor who!

Some of us have friends in and around research settings, and spend time discussing things with them, and also spend time discussing on sceptical boards. Also discussing with regular friends and family who may be sceptical about whether it's a psychological condition. These things drive us crackers of course, it's very frustrating. However what you very clearly learn from this - because they are ordinary people who you know well, and trust - is that there's no dark motive to their ignorance; they are simply ignorant. They know far, far less about it than us. Even the top scientists and retrovirologists in similar or vaguely related fields, know nothing whatsoever about CFS, and literally the only information they have seen at all is the two papers (Science and PNAS) - if you're very lucky! They haven't got time to look at anything else.

If you put facts like the above in front of them, they haven't got the time to check up on the sources and see if they're reliable - they will wait to see it in the BMJ, or the news, or whatever - until then, everything you've posted above is unverified rumour and they disregard it completely. That's just how they operate. We, on the other hand, have been delving into all this detail for a year, and detail of CFS for decades in some cases. Some of us may have no relevant qualifications, but we understand what we read. In simple terms: we really do know far more about it than they do! I know it sounds crazy, but it's true. Honestly! We have less context for all these facts than they do, but they haven't even seen these facts. They don't watch every Mikovits interview and transcribe every word for forensic group examination. We are way ahead of them. Don't feel bad about it, treat it as an opportunity. When the vindication comes...well, who doesn't like to say "I told you so"? Please don't be paranoid or sceptical or angry with this good doctor - he's exactly the kind of person we need on board. Bear in mind that while we know a lot more about CFS and XMRV than he does, he knows vastly more about retrovirology in general, and a whole host of other subjects besides. CFS is just one tiny drop in an ocean of knowledge for such people. That's all that's going on here.

Former CEO

One more thing Sunshine, it's also about sources of information. You talk to these people and if it ain't in PubMed, it don't exist. Period. They trust the BMJ, maybe certain columns, papers, online sources, and those are all colonised by the status quo psychiatric lobby. They would never see the info we see. The WPI site - what is that to them? It could be a hoax set up by some weird American group as far as they're concerned. Living in another world, that's all there is to it.

Senior Member

Thank you for sharing this. How nice of him to respond in detail like that. It's interesting to hear the perspective of a retrovirologist who hasn't really been involved, and to find out how the news is percolating out in the research community.

Senior Member

An excellent summary of some very pertinent facts. The only thing I disagree with is your interpretation of what it means that you know more about it than doctor who!

Some of us have friends in and around research settings, and spend time discussing things with them, and also spend time discussing on sceptical boards. Also discussing with regular friends and family who may be sceptical about whether it's a psychological condition. These things drive us crackers of course, it's very frustrating. However what you very clearly learn from this - because they are ordinary people who you know well, and trust - is that there's no dark motive to their ignorance; they are simply ignorant. They know far, far less about it than us. Even the top scientists and retrovirologists in similar or vaguely related fields, know nothing whatsoever about CFS, and literally the only information they have seen at all is the two papers (Science and PNAS) - if you're very lucky! They haven't got time to look at anything else.

If you put facts like the above in front of them, they haven't got the time to check up on the sources and see if they're reliable - they will wait to see it in the BMJ, or the news, or whatever - until then, everything you've posted above is unverified rumour and they disregard it completely. That's just how they operate. We, on the other hand, have been delving into all this detail for a year, and detail of CFS for decades in some cases. Some of us may have no relevant qualifications, but we understand what we read. In simple terms: we really do know far more about it than they do! I know it sounds crazy, but it's true. Honestly! We have less context for all these facts than they do, but they haven't even seen these facts. They don't watch every Mikovits interview and transcribe every word for forensic group examination. We are way ahead of them. Don't feel bad about it, treat it as an opportunity. When the vindication comes...well, who doesn't like to say "I told you so"? Please don't be paranoid or sceptical or angry with this good doctor - he's exactly the kind of person we need on board. Bear in mind that while we know a lot more about CFS and XMRV than he does, he knows vastly more about retrovirology in general, and a whole host of other subjects besides. CFS is just one tiny drop in an ocean of knowledge for such people. That's all that's going on here.

Well said, and I agree. I also think that we shouldn't assume that everyone in the patient community views the XMRV/MLV research the same way. Some are not as convinced as others that it's going to be the answer to ME/CFS, and that doesn't mean that they aren't just as concerned, just as sincere, and just as sick. I don't see any reason to think this post is a hoax or part of a conspiracy. As you pointed out, this researcher probably hasn't read through all the studies in depth (as most of us have). I'm pleased he's as informed as he is. After all, his field is HIV, not MLV. I was hoping that the Alter/Lo study might put the contamination question to rest, though.

disjecta membra

Emotionally, I'm still sceptical about XMRV... but it would be really hard to explain two positive papers without there being some link. Maybe it will just be far more complicated than the conneciton between HIV and AIDS (well - it must be with so many healthy positives).

There are healthy positives with HIV too. They are called "elite controllers." They are HIV positive but they never develop AIDS. It's a very small percentage of HIV positive people, and they appear to have some unique genetic characteristics that makes this possible, and they are heavily studied for clues into how their bodies control the virus and whether this information can be used for HIV treatments or vaccines.

No virus makes 100% of the people who get it sick.

With the HGRV group of viruses, the "healthy positives" will be worth looking at closely, to see if they ever develop disease - and if they don't, why they don't.

* XMRV is only found in laboratory mice fiddled with by scientists (See Dr Coffin's comments).
* Animal CELLS from laboratories have previously entered the human blood supply through government vaccination programmes. See HIV/Polio.
* XMRV/MULV is found in ME/CFS patients in very high numbers, who just happen to have neuro immune disease:

These percentage rates are this high, before even knowing the virus reservoir! (knowing where to look). Once knowing where to look they will of course be higher. (We need in addition to blood: tissue/CSF fluid tests to measure XMRV/MULV's, these have not been done yet in ME/CFS. The % findings are in their infancy and will only rise.

*XMRV has more positive studies coming out in 48hrs and the near future showing strong correlation to ME/CFS.

Blomberg
De Meirleir
Mikovits
Cheney
Another that Cort mentioned

*Contamination theory has been disproven by the CDC's Switzer back in 2009, and FDA in 2010.
This was important as due to being PCR, it could have been contamination (if not disproved, which it was). PCR is 'old hat', we now have other methods......

1)
We have CULTURE method to look for MULV/XMRV, and we have ANTIBODIES. Culture method takes your own fresh cell, and infects it with your own blood. Proving this is not contamination but a retrovirus living in your body infecting your own cells. End of argument.

2)
We have Antibody assays. It is physically impossible to have an antibody response to a contaminant.
So for the last time.... XMRV/MULV ANTIBODIES found in ME/CFS patients blood CANNOT BE CONTAMINATION.

If I know this and have no qualifications, this email from Rebecca_________ seems possible it could be a hoax to fool people who don't know basic science?

This Rebecca_______ email also comes on the eve of the 1st International Conference on XMRV that is about to reveal more and more direct links to XMRV/MULV's in ME/CFS

Make of that what you will.....either way it's too late. Everyone knows. Even uneducated people like me know. If I can understand then someone studying science for 35 years who has a Ph. D. in Biochemistry and Biophysics would know too.

Hi guys. This is a real e-mail and the qualifications mentioned are his qualifications. He is a professor now and he did his previous work on HIV and simbian retroviruses. He admits he did not read the recent report on the NIH and FDA findings and has not worked on any of the studies involving XMRV or MuLv reroviruses. I think he is planning to listen to the conference they are having in a few days and catch up then. I just thought it was very nice of him to write me back with such a detailed e-mail. I agree that they have sufficiently proven that contamination was not a problem. I also think that the FDA-NIH study has proved that this virus has evolved and there are many variants. I did not use his name because I was not sure he would want the added attention. It is interesting to hear what other doctors/scientists who have worked in the retrovirus fields believe about MuLv related retroviruses. Hopefully, after the conferance, they will know much more and become more interested.

P.S. I am not good at interpreting the journals or understanding the medical information surrounding XMRV, HGRV, MuLv related viruses, etc. If anyone can think of better questions to ask him (after the conference), please let me know.

Dr. Who is a popular British sci-fi/children's TV show that's been running for 30 years or more. You can often catch old episodes in the US on PBS stations.

He lives in police box (looks like an old wooden phone booth), which doubles as a space ship that travels through time. He battles various aliens/monsters who are trying to attack earth. The doctor morphs into a new body every 5 years or so (ie played by a new actor), which is how they keep the series fresh. Lots of cheesy special effects and monsters in rubber suits, at least on the older episodes. The Doctor is kind of bumbling, but brilliant at the same time. Fun stuff.

Senior Member

thanks for saying this, it is obvious but easily forgotten, bears repeating over and over in this context.

ETA:
"The prevalence of HIV infection in Washington, DC, is at least 3% among people aged over 12 years, as high as that in several African countries, a report by the District of Columbia's health department says ... The true prevalence may actually be higher, the report from the Washington Health Department says, because studies indicate that a third to a half of those infected do not know they are infected." http://www.medscape.com/viewarticle/590131

I know nothing

Mark good points made and nothing more to add exempt, i was astonished how little Alter himself knows about the topic ME/CFS and many more, who are involved in the recent ongoing research of XMRV. I posted passages of transcripts here a few weeks ago about the blood bank conference in May . It was astounding to hear with what nonchalance they talked about ME/CFS and how little they actually knew about ME. In time these researcher will get to know us patients and will catch hopefully up on 4000 research papers on ME/CFS from the last 25 years !

Former CEO

Dr. Who is a popular British sci-fi/children's TV show that's been running for 30 years or more. You can often catch old episodes in the US on PBS stations.

He lives in police box (looks like an old wooden phone booth), which doubles as a space ship that travels through time. He battles various aliens/monsters who are trying to attack earth. The doctor morphs into a new body every 5 years or so (ie played by a new actor), which is how they keep the series fresh. Lots of cheesy special effects and monsters in rubber suits, at least on the older episodes. The Doctor is kind of bumbling, but brilliant at the same time. Fun stuff.

That's just the TV show about him. The real Doctor Who is a Time Lord from the planet Gallifrey, who travels in the TARDIS (Time And Relative Dimensions In Space) and defends earth from external threats. His TARDIS only looks like a police box because its camoflage mechanism is bust. We would be lost without him.